Table of Contents Author Guidelines Submit a Manuscript
Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 5724046, 17 pages
https://doi.org/10.1155/2017/5724046
Research Article

Differential Regulation of Cardiac Function and Intracardiac Cytokines by Rapamycin in Healthy and Diabetic Rats

1Department of Medicine, University of Missouri, Columbia, MO, USA
2Harry S. Truman Memorial Veterans Affairs Hospital, Columbia, MO, USA
3Novopyxis, Boston, MA, USA
4Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, USA

Correspondence should be addressed to Lakshmi Pulakat; ude.iruossim.htlaeh@ltakalup

Received 12 November 2016; Revised 17 January 2017; Accepted 14 February 2017; Published 20 March 2017

Academic Editor: Anindita Das

Copyright © 2017 Christian Luck et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. B. K. Kennedy and D. W. Lamming, “The mechanistic target of rapamycin: the grand ConducTOR of metabolism and aging,” Cell Metabolism, vol. 23, no. 6, pp. 990–1003, 2016. View at Publisher · View at Google Scholar · View at Scopus
  2. T. Nacarelli and C. Sell, “Targeting metabolism in cellular senescence, a role for intervention,” Molecular and Cellular Endocrinology, 2016. View at Publisher · View at Google Scholar
  3. D. W. Lamming, “Inhibition of the mechanistic target of rapamycin (mTOR)—Rapamycin and beyond,” Cold Spring Harbor Perspectives in Medicine, vol. 6, no. 5, Article ID a025924, 2016. View at Publisher · View at Google Scholar · View at Scopus
  4. S. Sengupta, T. R. Peterson, and D. M. Sabatini, “Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress,” Molecular Cell, vol. 40, no. 2, pp. 310–322, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. R. Zoncu, A. Efeyan, and D. M. Sabatini, “MTOR: from growth signal integration to cancer, diabetes and ageing,” Nature Reviews Molecular Cell Biology, vol. 12, no. 1, pp. 21–35, 2011. View at Publisher · View at Google Scholar · View at Scopus
  6. R. D. Hannan, A. Jenkins, A. K. Jenkins, and Y. Brandenburger, “Cardiac hypertrophy: a matter of translation,” Clinical and Experimental Pharmacology and Physiology, vol. 30, no. 8, pp. 517–527, 2003. View at Publisher · View at Google Scholar · View at Scopus
  7. R. Gul, V. G. DeMarco, J. R. Sowers, A. Whaley-Connell, and L. Pulakat, “Regulation of overnutrition-induced cardiac inflammatory mechanisms,” Cardiorenal Medicine, vol. 2, no. 3, pp. 225–233, 2012. View at Publisher · View at Google Scholar
  8. L. Pulakat, V. G. DeMarco, S. Ardhanari et al., “Adaptive mechanisms to compensate for overnutrition-induced cardiovascular abnormalities,” American Journal of Physiology—Regulatory Integrative and Comparative Physiology, vol. 301, no. 4, pp. R885–R895, 2011. View at Publisher · View at Google Scholar · View at Scopus
  9. R. Gul, A. Mahmood, C. Luck et al., “Regulation of cardiac miR-208a, an inducer of obesity, by rapamycin and nebivolol,” Obesity, vol. 23, no. 11, pp. 2251–2259, 2015. View at Publisher · View at Google Scholar · View at Scopus
  10. A. Perl, “mTOR activation is a biomarker and a central pathway to autoimmune disorders, cancer, obesity, and aging,” Annals of the New York Academy of Sciences, vol. 1346, no. 1, pp. 33–44, 2015. View at Publisher · View at Google Scholar · View at Scopus
  11. D. E. Harrison, R. Strong, Z. D. Sharp et al., “Rapamycin fed late in life extends lifespan in genetically heterogeneous mice,” Nature, vol. 460, no. 7253, pp. 392–395, 2009. View at Publisher · View at Google Scholar · View at Scopus
  12. R. A. Miller, D. E. Harrison, C. M. Astle et al., “Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice,” Journals of Gerontology—Series A Biological Sciences and Medical Sciences, vol. 66, no. 2, pp. 191–201, 2011. View at Publisher · View at Google Scholar · View at Scopus
  13. A. Salmon, “Beyond diabetes: does obesity-induced oxidative stress drive the aging process?” Antioxidants, vol. 5, no. 3, p. E24, 2016. View at Publisher · View at Google Scholar
  14. A. Das, D. Durrant, S. Koka, F. N. Salloum, L. Xi, and R. C. Kukreja, “Mammalian target of rapamycin (mTOR) inhibition with rapamycin improves cardiac function in type 2 diabetic mice: potential role of attenuated oxidative stress and altered contractile protein expression,” Journal of Biological Chemistry, vol. 289, no. 7, pp. 4145–4160, 2014. View at Publisher · View at Google Scholar · View at Scopus
  15. A. Das, F. N. Salloum, S. M. Filippone et al., “Inhibition of mammalian target of rapamycin protects against reperfusion injury in diabetic heart through STAT3 signaling,” Basic Research in Cardiology, vol. 110, no. 3, article 31, 2015. View at Publisher · View at Google Scholar · View at Scopus
  16. K. Sataranatarajan, Y. Ikeno, A. Bokov et al., “Rapamycin increases mortality in db/db mice, a mouse model of type 2 diabetes,” The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, vol. 71, no. 7, pp. 850–857, 2016. View at Publisher · View at Google Scholar · View at Scopus
  17. N. Arnold, P. R. Koppula, R. Gul, C. Luck, and L. Pulakat, “Regulation of cardiac expression of the diabetic marker microRNA miR-29,” PLoS ONE, vol. 9, no. 7, Article ID e103284, 2014. View at Publisher · View at Google Scholar · View at Scopus
  18. K. Dionne, R. L. Redfern, J. J. Nichols et al., “Analysis of tear inflammatory mediators: a comparison between the microarray and luminex methods,” Molecular Vision, vol. 22, pp. 177–188, 2016. View at Google Scholar · View at Scopus
  19. Raybiotech, Quantibody® Rat Cytokine Array 67.
  20. H. Wickham, ggplot2: Elegant Graphics for Data Analysis, Springer, New York, NY, USA, 2009.
  21. W.-M. Huang, P.-F. Hsu, H.-M. Cheng et al., “Determinants and prognostic impact of hyperuricemia in hospitalization for acute heart failure,” Circulation Journal, vol. 80, no. 2, pp. 404–410, 2016. View at Publisher · View at Google Scholar · View at Scopus
  22. A. Daniels, D. Linz, M. Van Bilsen et al., “Long-term severe diabetes only leads to mild cardiac diastolic dysfunction in Zucker diabetic fatty rats,” European Journal of Heart Failure, vol. 14, no. 2, pp. 193–201, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. M. Ricke-Hoch, I. Bultmann, B. Stapel et al., “Opposing roles of Akt and STAT3 in the protection of the maternal heart from peripartum stress,” Cardiovascular Research, vol. 101, no. 4, pp. 587–596, 2014. View at Publisher · View at Google Scholar · View at Scopus
  24. X.-G. Chen, F. Liu, X.-F. Song et al., “Rapamycin regulates Akt and ERK phosphorylation through mTORC1 and mTORC2 signaling pathways,” Molecular Carcinogenesis, vol. 49, no. 6, pp. 603–610, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. B. W. Van Tassell, J. M. V. Raleigh, and A. Abbate, “Targeting interleukin-1 in heart failure and inflammatory heart disease,” Current Heart Failure Reports, vol. 12, no. 1, pp. 33–41, 2015. View at Publisher · View at Google Scholar · View at Scopus
  26. H. B. Sager, T. Heidt, M. Hulsmans et al., “Targeting interleukin-1β reduces leukocyte production after acute myocardial infarction,” Circulation, vol. 132, no. 20, pp. 1880–1890, 2015. View at Publisher · View at Google Scholar · View at Scopus
  27. H. Peng, Z. Sarwar, X.-P. Yang et al., “Profibrotic role for interleukin-4 in cardiac remodeling and dysfunction,” Hypertension, vol. 66, no. 3, pp. 582–589, 2015. View at Publisher · View at Google Scholar · View at Scopus
  28. Z. Zeng, K. Yu, L. Chen, W. Li, H. Xiao, and Z. Huang, “Interleukin-2/anti-interleukin-2 immune complex attenuates cardiac remodeling after myocardial infarction through expansion of regulatory T cells,” Journal of Immunology Research, vol. 2016, Article ID 8493767, 13 pages, 2016. View at Publisher · View at Google Scholar · View at Scopus
  29. S. P. Jones, S. D. Trocha, and D. J. Lefer, “Cardioprotective actions of endogenous IL-10 are independent of iNOS,” American Journal of Physiology—Heart and Circulatory Physiology, vol. 281, no. 1, pp. H48–H52, 2001. View at Google Scholar · View at Scopus
  30. K. Kawamura, K. Iyonaga, H. Ichiyasu, J. Nagano, M. Suga, and Y. Sasaki, “Differentiation, maturation, and survival of dendritic cells by osteopontin regulation,” Clinical and Diagnostic Laboratory Immunology, vol. 12, no. 1, pp. 206–212, 2005. View at Publisher · View at Google Scholar · View at Scopus
  31. A. M. Feldman, A. Combes, D. Wagner et al., “The role of tumor necrosis factor in the pathophysiology of heart failure,” Journal of the American College of Cardiology, vol. 35, no. 3, pp. 537–544, 2000. View at Publisher · View at Google Scholar · View at Scopus
  32. D. S. Cross, C. A. McCarty, E. Hytopoulos et al., “Coronary risk assessment among intermediate risk patients using a clinical and biomarker based algorithm developed and validated in two population cohorts,” Current Medical Research and Opinion, vol. 28, no. 11, pp. 1819–1830, 2012. View at Publisher · View at Google Scholar · View at Scopus
  33. J. J. Carrero, J. Kyriazis, A. Sonmez et al., “Prolactin levels, endothelial dysfunction, and the risk of cardiovascular events and mortality in patients with CKD,” Clinical Journal of the American Society of Nephrology, vol. 7, no. 2, pp. 207–215, 2012. View at Publisher · View at Google Scholar · View at Scopus
  34. A. Boufenzer, J. Lemarié, T. Simon et al., “TREM-1 mediates inflammatory injury and cardiac remodeling following myocardial infarction,” Circulation Research, vol. 116, no. 11, pp. 1772–1782, 2015. View at Publisher · View at Google Scholar · View at Scopus
  35. I. Kogan-Sakin, M. Cohen, N. Paland et al., “Prostate stromal cells produce CXCL-1, CXCL-2, CXCL-3 and IL-8 in response to epithelia-secreted IL-1,” Carcinogenesis, vol. 30, no. 4, pp. 698–705, 2009. View at Publisher · View at Google Scholar · View at Scopus
  36. M. Tomaszewski, F. J. Charchar, C. P. Nelson et al., “Pathway analysis shows association between FGFBP1 and hypertension,” Journal of the American Society of Nephrology, vol. 22, no. 5, pp. 947–955, 2011. View at Publisher · View at Google Scholar · View at Scopus
  37. J. Jahanyar, D. L. Joyce, R. E. Southard et al., “Decorin-mediated transforming growth factor-β inhibition ameliorates adverse cardiac remodeling,” The Journal of Heart and Lung Transplantation, vol. 26, no. 1, pp. 34–40, 2007. View at Publisher · View at Google Scholar · View at Scopus
  38. Y. Wang, Y. Cao, S. Yamada et al., “Cardiomyopathy and Worsened Ischemic Heart Failure in SM22-α Cre-Mediated Neuropilin-1 Null Mice: Dysregulation of PGC1α and Mitochondrial Homeostasis,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 35, no. 6, pp. 1401–1412, 2015. View at Publisher · View at Google Scholar · View at Scopus
  39. J. C. Schisler, R. Schuck, X. Dai et al., “Clinical evidence of a protective role for CXCL5 in coronary artery disease progression in the elderly,” The FASEB Journal, vol. 30, no. 1, supplement 1177.17, 2016. View at Google Scholar
  40. S. P. Levick and P. H. Goldspink, “Could interferon-gamma be a therapeutic Target for treating heart failure?” Heart Failure Reviews, vol. 19, no. 2, pp. 227–236, 2014. View at Publisher · View at Google Scholar · View at Scopus
  41. G. F. Pierce, J. E. Tarpley, J. Tseng et al., “Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF-BB and absence of PDGF in chronic nonhealing wounds,” Journal of Clinical Investigation, vol. 96, no. 3, pp. 1336–1350, 1995. View at Publisher · View at Google Scholar · View at Scopus
  42. B. McCright, J. Lozier, and T. Gridley, “A mouse model of Alagille syndrome: Notch2 as a genetic modifier of Jag1 haploinsufficiency,” Development, vol. 129, no. 4, pp. 1075–1082, 2002. View at Google Scholar · View at Scopus
  43. H. Jin, J. M. Wyss, R. Yang, and R. Schwall, “The therapeutic potential of hepatocyte growth factor for myocardial infarction and heart failure,” Current Pharmaceutical Design, vol. 10, no. 20, pp. 2525–2533, 2004. View at Publisher · View at Google Scholar · View at Scopus
  44. M. F. Brizzi, L. Formato, P. Dentelli et al., “Interleukin-3 stimulates migration and proliferation of vascular smooth muscle cells: a potential role in atherogenesis,” Circulation, vol. 103, no. 4, pp. 549–554, 2001. View at Publisher · View at Google Scholar · View at Scopus
  45. A. Q. Reuwer, M. T. B. Twickler, B. A. Hutten et al., “Prolactin levels and the risk of future coronary artery disease in apparently healthy men and women,” Circulation: Cardiovascular Genetics, vol. 2, no. 4, pp. 389–395, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. A. Wilhelm, E. L. Shepherd, A. Amatucci et al., “Interaction of TWEAK with Fn14 leads to the progression of fibrotic liver disease by directly modulating hepatic stellate cell proliferation,” Journal of Pathology, vol. 239, no. 1, pp. 109–121, 2016. View at Publisher · View at Google Scholar · View at Scopus
  47. X. Shi, M. Zhang, F. Liu et al., “Tim-1-Fc suppresses chronic cardiac allograft rejection and vasculopathy by reducing IL-17 production,” International Journal of Clinical and Experimental Pathology, vol. 7, no. 2, pp. 509–520, 2014. View at Google Scholar · View at Scopus
  48. R. Spagnuolo, M. Corada, F. Orsenigo et al., “Gas1 is induced by VE-cadherin and vascular endothelial growth factor and inhibits endothelial cell apoptosis,” Blood, vol. 103, no. 8, pp. 3005–3012, 2004. View at Publisher · View at Google Scholar · View at Scopus
  49. S. I. Arriola Apelo, J. C. Neuman, E. L. Baar et al., “Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system,” Aging Cell, vol. 15, no. 1, pp. 28–38, 2016. View at Publisher · View at Google Scholar · View at Scopus
  50. J. M. Flynn, M. N. O'Leary, C. A. Zambataro et al., “Late-life rapamycin treatment reverses age-related heart dysfunction,” Aging Cell, vol. 12, no. 5, pp. 851–862, 2013. View at Publisher · View at Google Scholar · View at Scopus
  51. R. F. Mapanga and M. F. Essop, “Damaging effects of hyperglycemia on cardiovascular function: spotlight on glucose metabolic pathways,” American Journal of Physiology—Heart and Circulatory Physiology, vol. 310, no. 2, pp. H153–H173, 2016. View at Publisher · View at Google Scholar · View at Scopus
  52. J. Shi, J. Li, H. Guan et al., “Anti-fibrotic actions of interleukin-10 against hypertrophic scarring by activation of PI3K/AKT and STAT3 signaling pathways in scar-forming fibroblasts,” PLoS ONE, vol. 9, no. 5, article e98228, 2014. View at Publisher · View at Google Scholar · View at Scopus
  53. J. Shi, J. Li, H. Guan et al., “Anti-fibrotic actions of interleukin-10 against hypertrophic scarring by activation of PI3K/AKT and STAT3 signaling pathways in scar-forming fibroblasts,” PLoS ONE, vol. 9, no. 5, Article ID e98228, 2014. View at Publisher · View at Google Scholar · View at Scopus
  54. M. S. Wilson, E. Elnekave, M. M. Mentink-Kane et al., “IL-13Rα2 and IL-10 coordinately suppress airway inflammation, airway-hyperreactivity, and fibrosis in mice,” Journal of Clinical Investigation, vol. 117, no. 10, pp. 2941–2951, 2007. View at Publisher · View at Google Scholar · View at Scopus
  55. S. D. Oldroyd, G. L. Thomas, G. Gabbiani, and A. Meguid El Nahas, “Interferon-γ inhibits experimental renal fibrosis,” Kidney International, vol. 56, no. 6, pp. 2116–2127, 1999. View at Publisher · View at Google Scholar · View at Scopus
  56. H. Emmez, O. Kardes, F. Dogulu, G. Kurt, L. Memis, and M. K. Baykaner, “Role of antifibrotic cytokine interferon-γ in the prevention of postlaminectomy peridural fibrosis in rats,” Neurosurgery, vol. 62, no. 6, pp. 1351–1357, 2008. View at Google Scholar · View at Scopus
  57. B. B. Moore, M. J. Coffey, P. Christensen et al., “GM-CSF regulates bleomycin-induced pulmonary fibrosis via a prostaglandin-dependent mechanism,” Journal of Immunology, vol. 165, no. 7, pp. 4032–4039, 2000. View at Publisher · View at Google Scholar · View at Scopus
  58. F. Chirillo, F. Bacchion, A. Pedrocco et al., “Infective endocarditis in patients with diabetes mellitus,” Journal of Heart Valve Disease, vol. 19, no. 3, pp. 312–320, 2010. View at Google Scholar · View at Scopus
  59. L. M. A. J. Muller, K. J. Gorter, E. Hak et al., “Increased risk of common infections in patients with type 1 and type 2 diabetes mellitus,” Clinical Infectious Diseases, vol. 41, no. 3, pp. 281–288, 2005. View at Publisher · View at Google Scholar · View at Scopus
  60. M. L. Davila, Y. Fu, J. Yang et al., “Role of CCR10 and CCL27 in skin resident T cell development and homeostasis,” The Journal of Immunology, vol. 196, no. 1, supplement, p. 137.7, 2016. View at Google Scholar
  61. C. Yang, B. Chen, J. Zhao et al., “TREM-1 signaling promotes host defense during the early stage of infection with highly pathogenic Streptococcus suis,” Infection and Immunity, vol. 83, no. 8, pp. 3293–3301, 2015. View at Publisher · View at Google Scholar · View at Scopus
  62. J. A. Suaya, D. F. Eisenberg, C. Fang, and L. G. Miller, “Skin and soft tissue infections and associated complications among commercially insured patients aged 0–64 years with and without diabetes in the U.S,” PLoS ONE, vol. 8, no. 4, Article ID e60057, 2013. View at Publisher · View at Google Scholar · View at Scopus
  63. N. Gude and M. Sussman, “Notch signaling and cardiac repair,” Journal of Molecular and Cellular Cardiology, vol. 52, no. 6, pp. 1226–1232, 2012. View at Publisher · View at Google Scholar · View at Scopus
  64. A. Mahmood and L. Pulakat, “Differential effects of β-blockers, Angiotensin II receptor blockers, and a novel AT2R agonist NP-6A4 on stress response of nutrient-starved cardiovascular cells,” PLoS ONE, vol. 10, no. 12, Article ID e0144824, 2015. View at Publisher · View at Google Scholar · View at Scopus